Brain Pathology Case of the Month - September 2007

DIAGNOSIS:

STROMA POOR GANGLIONEUROBLASTOMA OF SYMPATHETIC GANGLION

DISCUSSION:

Peripheral ganglioneuroblastomas are common tumors in childhood, presenting as posterior mediastinal paravertebral tumors, at times extending intraspinally along the canal to cause cord compression. They are a relatively homogenous group of tumors in their encapsulation, silent growth, relatively large size, biochemical inactivity and better long term survival unlike peripheral neuroblastomas (5). These tumors of neuronal lineage arise from dorsal root ganglia and paravertebral autonomic ganglia in addition to the adrenal medulla, which is the most common site of origin (6). We present a case of paraspinal ganglioneuroblastoma extending into the extradural space of the dorsal spinal canal through intervertebral foramina, presenting as a neurological emergency and mistaken for a nerve sheath tumor.

In contrast to central neuroblastomas, the peripheral neuroblastic tumors have a cellular origin from neural crest and are ontogenically related to the sympathetic nervous system. Most primary tumors occur in the abdomen. In children they frequently arise in adrenal medulla, while in infants thoracic and cervical location is preferred. Because of their origin in the paravertebral sites, the ganglioneuroblastomas tend to invade through neural foramina into the spinal canal, causing cord compression and can be mistaken for nerve sheath tumors. As the treatment requires extensive laminectomy and radiation to the spine, which can result in long term morbidity later in life, chemotherapy is considered a safe and effective initial modality of management.

Spontaneous regression and terminal maturation to ganglionic element from neuroblastic stage with favorable outcome is peculiar to these tumors, as was noted in the present case. The factors responsible for regulating neural differentiation are not well understood, but probably involve one or several ligand-receptor pathways like the NGF receptor genes - NTRKs and suppression of the proto-oncogene N-myc, conferring a better prognosis (1, 2, 3, 4). On histology, increased mitosis and karyorrhectic activity reflect poor prognosis, while ganglionic differentiation, neurite formation and abundant neurofibrillary material in the midst of undifferentiated cells reflect good prognosis, as noted in the present case. Expression of the progenitor cell marker, nestin in the immature ganglion cells probably indicate the transition of the tumor from ontogenetically highly immature neuroepithelial cell to relatively maturing cell, but may not reflect the biological behavior or persistence of stem cell population. In the pediatric age, ganglioneuroblastoma is an important condition to be considered in treating paravertebral mass lesions with neurologic deficits and aggressive therapeutic approach is useful in management.